Classifications

• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
  • A61K31/00—Medicinal preparations containing organic active ingredients
  • A61K31/33—Heterocyclic compounds
  • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
  • A61K31/535—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with at least one nitrogen and one oxygen as the ring hetero atoms, e.g. 1,2-oxazines
  • A61K31/5375—1,4-Oxazines, e.g. morpholine
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/14—Drugs for disorders of the nervous system for treating abnormal movements, e.g. chorea, dyskinesia
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/20—Hypnotics; Sedatives
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
  • A61P25/32—Alcohol-abuse
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
  • A61P25/34—Tobacco-abuse
• • A—HUMAN NECESSITIES
  • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
  • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
  • A61P25/00—Drugs for disorders of the nervous system
  • A61P25/30—Drugs for disorders of the nervous system for treating abuse or dependence
  • A61P25/36—Opioid-abuse

Definitions

• This invention describes new treatments for several nervous system disorders, including: Addictive Disorders, Psychoactive Substance Use Disorders, Nicotine Addiction or Tobacco Addiction resulting in Smoking Cessation and Attention Deficit Hyperactivity Disorder (ADHD).
• the treatment involves the administration of the drug Reboxetine to a patient in need.
• Desipramine for example, has been characterized as “one of the most studied of the tricyclic anti-depressants in ADHD children and adolescents.” T. E. Wilens, et al. Am. J. Psychiatry 153:1147-1153, 1148 (1996). It has also been considered as a treatment for the disease in adults. Id. Unfortunately, a lack of selectivity for most tricyclics, including desipramine can also cause undesired side effects particularly on the acetylcholine (especially the muscarinic component), and histamine mediated neurotransmission.
• methylphenidate Another drug, methylphenidate, is also known to have clinical efficacy for the treatment of ADHD. Wender, P. H., et al. Am. J. Psychiatry 142:547-552 (1985).
• SSRI serotonin
• NA noradrenaline
• This patent application describes the treatment of Addictive Disorders, Psychoactive Substance Use Disorders, Nicotine Addition or Tobacco Addiction (with a result of Smoking Cessation or a decrease in smoking) and Attention Deficit Hyperactivity Disorder (ADHD), comprising administering a therapeutically effective, nontoxic dose of Reboxetine and derivatives and or pharmaceutically acceptable salts thereof to a patient.
• ADHD Attention Deficit Hyperactivity Disorder
• Reboxetine is the generic name of the pharmaceutical substance with the chemical name of 2-(I-((2-ethoxyphenoxy)benzyl)-morpholine, and its pharmaceutically acceptable salts.
• Reboxetine can be a free base, or it can include reboxetine methanesulfonate (also called reboxetine mesylate) or any other pharmaceutically acceptable salt that does not significantly affect the pharmaceutical activity of the substance.
• a preferred dose range is 4 to 10 mg per patient per day and the most preferred dose is 6 to 8 mg or 8 to 10 mg per patient daily, depending upon the patient, delivered twice a day (b.i.d.).
• Reboxetine is the generic name of the pharmaceutical substance with the chemical name of 2-(I-((2-ethoxyphenoxy)benzyl)-morpholine, and its pharmaceutically acceptable salts.
• Reboxetine can be a free base, or it can include reboxetine methanesulfonate (also called reboxetine mesylate) or any other pharmaceutically acceptable salt that does not significantly affect the pharmaceutical activity of the substance.
• Reboxetine and a method of synthesis are described in U.S. Pat. No. 4,229,449, issued Oct. 21, 1980, Melloni et. al., incorporated by reference, methods of preparation are described in U.S. 5,068,433, issued Nov. 26, 1991, Melloni et. al. and in U.S. Pat. No. 5,391,735, issued Feb. 21, 1995, both incorporated by reference.
• Reboxetine may also be known under the trade name of EDRONAXTM.
• Reboxetine acts as an antidepressant.
• Antidepressants are frequently grouped into categories or “generations.”
• the first generation of antidepressants were usually tricyclic antidepressants such as maprotiline that affected various neurotransmitter systems and are associated with many undesirable side effects.
• the second generation of antidepressants, such as mianserine, mirtrazapine and trazodone are largely devoid of anticholinergic action and their adrenolytic and antihistaminic effects are weaker.
• antidepressants e.g.
• SSRI ipsapirone, viloxazine, reboxetine, bupropione
• SSRI ipsapirone, viloxazine, reboxetine, bupropione
• 5-HT noradrenaline
• dopamine noradrenaline
• Reboxetine however; does not act like most antidepressants. Unlike tricyclic antidepressants and even selective serotonin reuptake inhibitors (SSRIs), reboxetine is ineffective in the 8-OH-DPAT hypothermia test, indicating that reboxetine is not a selective serotonin reuptake inhibitor rather it is selective for the noradrenergic system. Thus, reboxetine is not an SSRI, rather it is considered a novel, selective, noradrenaline-reuptake inhibitor (NARI). Leonard-BE, “Noradrenaline in basic models of depression.” European-Neuropsychopharmacol. April; 1997 7 Suppl 1: S11-6; discussion S71-3.
• NARI noradrenaline-reuptake inhibitor
• Reboxetine is a highly selective norepinephrine uptake inhibitor, with only marginal serotonin and no dopamine uptake inhibitory activity.
• the compound displays only weak or no anti-cholinergic activity in different animal models and is devoid of monoamine oxidase (MAO) inhibitory activity.
• MAO monoamine oxidase
• Reboxetine is highly potent and fast acting. Our investigations indicate Reboxetine has potent antireserpine activity and combines the inhibitory properties of classical tricyclic antidepressants on the reuptake of noradrenaline with an ability to desensitize J-adrenergic receptor function without showing any appreciable interaction with muscarinic cholinergic and I-adrenerigic receptors. Moreover, Reboxetine shows less vagolytic activity than other tricyclic antidepressants.
• Reboxetine has been found particularly useful for treating or enhancing the treatment of a few psychiatric symptoms or disorders, with greater efficacy and with fewer side effects, than are treated by known drugs. Furthermore, the inventors here have also discovered that Reboxetine can also be used to treat or to enhance the treatment of a few other specific psychiatric symptoms or disorders. The symptoms or disorders amenable to treatment with Reboxetine are provided below.
• the dosage used to treat all of the disorders described here is as follows.
• Reboxetine is well tolerated and has a wide safety range, it can be administered in a dose range of active ingredient from about 1 to over 20 mg/kg. It is more commonly provided in dosages of from 1 to 20 mg per patient per day.
• the compound may be administered by any suitable method including a convenient oral dosage form.
• a preferred method is oral dosing twice a day.
• the preferred dose range is 4 to 10 mg per patient per day and the most preferred dose is 6 to 8 mg or 8 to 10 mg per patient daily, depending upon the patient, delivered twice a day (b.i.d.).
• suitable administrations could be 4 mg in the morning and 2 or 4 mg in the evening or 6 mg in the morning and 4 mg in the evening.
• the ideal dosing would be 3-5 mg in the morning and 3-5 mg in the evening. A skilled practitioner would be expected to determine the precise level of dosing. The ideal dosing would be routinely determined by an evaluation of clinical trials and the needs of the patient.
• the diseases described for treatment here are:
• Addictive Disorders, Alcohol and Other Psychoactive Substance Use Disorders, disorders related to Intoxication and Inhalants and especially Tobacco Addiction or Nicotine Addiction may be treated with Reboxetine.
• Tobacco Addiction or Nicotine Addiction would be treated with Reboxetine in order to achieve smoking/chewing cessation or smoking/chewing reduction.
• General descriptions of Addictive Disorders, including disorders related to Intoxication and Inhalants and Tobacco Addiction or Nicotine Addiction may be found in many standard sources, such as, The American Psychiatric Press Textbook of Psychiatry, Second Edition, Edited by Robert E. Hales, Stuart C. Yudofsky, and John A. Talbott, copyright 1994, incorporated by reference, especially pp. 401 et. seq., section on “Nicotine” incorporated by reference. Another of many texts is the Manual of Psychiatric Therapeutics, Second Edition, edited by Richard I. Shader, incorporated by reference, especially pp. 85 from Chapter 11 (Hy
• Alcohol and Other Psychoactive Substance Use Disorders such as disorders related to Intoxication and Inhalants and Tobacco Addiction or Nicotine Addiction but especially Tobacco Addiction involves the administration of Reboxetine in a manner and form that provide a reduction in the symptoms of the disease.
• Tobacco Addiction or Nicotine Addiction in particular would be treated to achieve a reduction or cessation of smoking or chewing of nicotine containing materials by a patient.
• Cessation or a reduction in smoking or chewing of addictive or psychoactive substances involves the administration of Reboxetine in a manner and form that provide a reduction in the symptoms of the disease, or with Tobacco or Nicotine with a reduction in the amount smoked or chewed. See the general description above for administration of Reboxetine.
• ADHD Attention Deficit Hyperactivity Disorder
• ADHD is a condition or disease state that may be treated with Reboxetine.
• General descriptions of ADHD may be found in many standard sources, such as, The American Psychiatric Press Textbook of Psychiatry, Second Edition, Edited by Robert E. Hales, Stuart C. Yudofsky, and John A. Talbott, copyright 1994, incorporated by reference, especially pp. 741 et. al., section on “ADHD,” incorporated by reference.
• Another of many texts is the Manual of Psychiatric Therapeutics, Second Edition, edited by Richard I. Shader, incorporated by reference, especially Chapter 18, Attention-Deficit hyperactivity Disorder, and pp. 172 et. seq., incorporated by reference.
• Attention Deficit Hyperactivity Disorder involves the administration of Reboxetine in a manner and form that provide a reduction in the symptoms of the disease.
• a child or young adult may require a smaller dosage depending upon the size, age, condition of the patient. See general description above for administration of Reboxetine.

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• Chemical Kinetics & Catalysis (AREA)
• Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
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• Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
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• 1999
  • 1999-04-02 EA EA200001049A patent/EA200001049A1/ru unknown
  • 1999-04-02 WO PCT/US1999/004289 patent/WO1999052531A1/en active IP Right Grant
  • 1999-04-02 CZ CZ20003671A patent/CZ297346B6/cs not_active IP Right Cessation
  • 1999-04-02 JP JP2000543141A patent/JP2002511414A/ja not_active Withdrawn
  • 1999-04-02 IL IL13885599A patent/IL138855A0/xx unknown
  • 1999-04-02 DE DE69926616T patent/DE69926616T2/de not_active Expired - Fee Related
  • 1999-04-02 DK DK99916114T patent/DK1069900T3/da active
  • 1999-04-02 CN CN99804011A patent/CN1301164A/zh active Pending
  • 1999-04-02 PT PT99916114T patent/PT1069900E/pt unknown
  • 1999-04-02 KR KR1020007011158A patent/KR20010034758A/ko not_active Application Discontinuation
  • 1999-04-02 NZ NZ507398A patent/NZ507398A/en unknown
  • 1999-04-02 CA CA002321157A patent/CA2321157A1/en not_active Abandoned
  • 1999-04-02 AT AT99916114T patent/ATE301462T1/de not_active IP Right Cessation
  • 1999-04-02 PL PL99346293A patent/PL193797B1/pl unknown
  • 1999-04-02 ES ES99916114T patent/ES2244189T3/es not_active Expired - Lifetime
  • 1999-04-02 TR TR2000/02868T patent/TR200002868T2/xx unknown
  • 1999-04-02 BR BR9909478-9A patent/BR9909478A/pt not_active Application Discontinuation
  • 1999-04-02 AU AU34494/99A patent/AU756373B2/en not_active Ceased
  • 1999-04-02 SK SK1449-2000A patent/SK14492000A3/sk unknown
  • 1999-04-02 EP EP99916114A patent/EP1069900B1/en not_active Expired - Lifetime
  • 1999-04-02 CA CA002634698A patent/CA2634698A1/en not_active Abandoned
  • 1999-04-02 HU HU0102436A patent/HUP0102436A3/hu unknown
• 2000
  • 2000-05-05 US US09/565,780 patent/US6352986B1/en not_active Expired - Fee Related
  • 2000-08-28 ZA ZA200004454A patent/ZA200004454B/en unknown
  • 2000-10-06 NO NO20005059A patent/NO20005059D0/no not_active Application Discontinuation

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